6H6A

Crystal structure of UNC119 in complex with LCK peptide

Summary for 6H6A

• Entry DOI: 10.2210/pdb6h6a/pdb
• Descriptor: Protein unc-119 homolog A, GLY-CYS-GLY-CYS-SER-SER, GLYCEROL, ... (8 entities in total)
• Functional Keywords: complex, transport, kinase, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 70248.44

Authors

Yelland, T.,ElMaghloob, Y.,McIlwraith, M.,Stephen, L.,Ismail, S. (deposition date: 2018-07-26, release date: 2018-09-26, Last modification date: 2024-10-23)

Primary citation

Stephen, L.A.,ElMaghloob, Y.,McIlwraith, M.J.,Yelland, T.,Castro Sanchez, P.,Roda-Navarro, P.,Ismail, S.
The Ciliary Machinery Is Repurposed for T Cell Immune Synapse Trafficking of LCK.
Dev.Cell, 47:122-132.e4, 2018

PubMed Abstract: Upon engagement of the T cell receptor with an antigen-presenting cell, LCK initiates TCR signaling by phosphorylating its activation motifs. However, the mechanism of LCK activation specifically at the immune synapse is a major question. We show that phosphorylation of the LCK activating Y394, despite modestly increasing its catalytic rate, dramatically focuses LCK localization to the immune synapse. We describe a trafficking mechanism whereby UNC119A extracts membrane-bound LCK by sequestering the hydrophobic myristoyl group, followed by release at the target membrane under the control of the ciliary ARL3/ARL13B. The UNC119A N terminus acts as a "regulatory arm" by binding the LCK kinase domain, an interaction inhibited by LCK Y394 phosphorylation, thus together with the ARL3/ARL13B machinery ensuring immune synapse focusing of active LCK. We propose that the ciliary machinery has been repurposed by T cells to generate and maintain polarized segregation of signals such as activated LCK at the immune synapse.

PubMed: 30220567
DOI: 10.1016/j.devcel.2018.08.012

Experimental method

X-RAY DIFFRACTION (2 Å)